Participants will receive PENNVAX-G vaccine administered by intramuscular injection (IM) via Biojector 2000 needleless device in either deltoid on Days 0 and 28. They will then receive MVA-CMDR administered IM by needle and syringe in either deltoid on Days 84 and 168.

Participants will receive PENNVAX-G vaccine administered via CELLECTRA EP in either deltoid on Days 0 and 28. They will then receive MVA-CMDR administered IM by needle and syringe in either deltoid on Days 84 and 168.

Participants will receive PENNVAX-G vaccine administered IM via Biojector 2000 needleless device in either deltoid on Days 0 and 28. They will then receive MVA-CMDR administered IM by needle and syringe in either deltoid on Days 84 and 168.

Participants will receive placebo vaccine for PENNVAX-G administered IM via Biojector 2000 needless device in either deltoid on Days 0 and 28. They will then receive placebo vaccine for MVA-CMDR administered IM by needle and syringe in either deltoid on Days 84 and 168.

Biological: Placebo PENNVAX-G Vaccine

Sodium Chloride Injection USP, 0.9%

Biological: Placebo MVA-CMDR Vaccine

Sodium Chloride Injection USP, 0.9%

Experimental: Group 4: Subgroup 1

Participants will receive PENNVAX-G vaccine administered IM via CELLECTRA EP in either deltoid on Days 0 and 28. They will then receive MVA-CMDR administered IM by needle and syringe in either deltoid on Days 84 and 168.

Participants will receive placebo vaccine for PENNVAX-G administered IM via CELLECTRA EP in either deltoid on Days 0 and 28. They will then receive placebo vaccine for MVA-CMDR administered IM by needle and syringe in either deltoid on Days 84 and 168.

Biological: Placebo PENNVAX-G Vaccine

Sodium Chloride Injection USP, 0.9%

Biological: Placebo MVA-CMDR Vaccine

Sodium Chloride Injection USP, 0.9%

Detailed Description:

Despite advances in treatment, HIV/AIDS rates remain high in low- and middle-income countries in resource-limited areas of the world. Preventive HIV vaccines would be an effective way to decrease the spread of HIV/AIDS. This study will evaluate an experimental HIV preventive vaccine followed by booster: the PENNVAX-G DNA vaccine and the Modified Vaccinia Ankara-Chiang Mai Double Recombinant (MVA-CMDR) booster vaccine. The MVA virus is a mild form of a vaccinia virus that is used in smallpox vaccines and does not cause smallpox infection. It has been safely used in vaccines for many years. Study researchers will examine if the combination of the two vaccines will provide an effective way for the body to build a defense against HIV. The PENNVAX-G vaccine will be administered to participants using one of two devices—the Biojector 2000 needleless device or the CELLECTRA intramuscular (IM) electroporation (EP) device—to evaluate how the immune response to the vaccine changes based on the device that is used. The purpose of this study is to evaluate the safety and immunogenicity of the PENNVAX-G vaccine, administered by either Biojector 2000 injection or CELLECTRA EP, followed by an MVA-CMDR vaccine boost, in healthy, HIV-uninfected adults.

This study will be conducted in two parts. Participants in the first part of the study will attend a baseline study visit, and they will undergo blood and urine collection, a medical history review, physical examination, and HIV testing counseling. All participants will receive the PENNVAX-G vaccine at baseline and Day 28. They will be randomly assigned to receive the vaccine by either the Bioinjector 2000 needleless device or the CELLECTRA IM EP device. On Days 84 and 168, all participants will receive the MVA-CMDR vaccine by IM injection delivered via needle and syringe. Participants will remain in the clinic for 1 hour after each vaccination for observation and vital sign monitoring, and they will record their temperatures and any symptoms in a diary for 7 days after each vaccination. Study staff will contact participants 1 to 2 days after each vaccination for follow-up monitoring. In addition to the vaccination study visits, participants will attend study visits at Weeks 1, 2, 4, 5, 6, 13, 14, 25, 26, 37, 50, and 52 and will repeat the baseline study procedures.

At the conclusion of the first part of the study, participants' study data will be reviewed and the safety of the vaccine regimen will be determined. If the regimen is found to be safe, then the second part of the study will begin. Participants in the second part of the study will be randomly assigned to receive the PENNVAX-G vaccine administered by either the Bioinjector 2000 device or the CELLECTRA EP device at baseline and Day 28, followed by the MVA-CDMR boost at Days 84 and 168, or they will receive placebo PENNVAX-G vaccine administered by either the Bioinjector 2000 device or the CELLECTRA EP device at baseline and Day 28, followed by a placebo MVA-CDMR boost at Days 84 and 168. All study visits and procedures that occurred during the first part of the study will also take place in the second part of the study.

Participants in the second part of the study will have the option of enrolling in a substudy. The purpose of the substudy is to evaluate the antibody response of the reproductive tract mucosa to the PENNVAX-G DNA, MVA-CDMR, and placebo vaccines administered in the main part of study. The substudy will also evaluate the effectiveness of using the Instead Softcup as a collection method to collect vaginal secretions for testing. Mucosal specimens and urine samples will be collected from participants at the screening visit and during the Week 2, 6, 14, 26, and 50 study visits.

Assessed by the clinic staff as being at low risk of HIV infection on the basis of sexual behaviors within the 12 months prior to enrollment as follows: sexually abstinent, or had two or fewer mutually monogamous relationships with HIV-uninfected partners and who have not used illicit drugs, or had two or fewer partners believed to be HIV uninfected and who did not use illicit drugs and with whom he/she regularly uses condoms for sexual intercourse

Healthy men and women (determined by medical history, physical examination, and clinical judgment)

Available and willing to participate for 12 months for study visits and annual follow-up for 18 months after study completion

Must be willing to have photo or fingerprint taken for identification purposes

Must be willing to be taken home at enrollment visit and allow home visits, if needed

Able to read and willing to complete the informed consent process

Has the following laboratory criteria within 45 days prior to study entry:

Hemoglobin: Women: 11 mg/dL; Men: 12.5 mg/dL

White cell count: 2,500 to 11,000 cells/mm^3

Platelets: 125,000 to 450,000 per mm^3

Urinalysis: protein and blood less than 1+, glucose negative

Normal liver function tests to include alanine aminotransferase (ALT)/aspartate aminotransferase (AST), alkaline phosphatase, gamma-glutamyl transpeptidase (GGT) (less than or equal to 1.25 times the institutional upper limits of normal), creatine phosphokinase (CPK) (less than or equal to 600 IU/L), troponin I (less than 0.4 ng/mL), and creatinine (less than or equal to 1.25 times the institutional upper limits of normal)

Female participants must have a negative pregnancy test at the screening visit and have a negative pregnancy test immediately prior to each vaccine/placebo vaccination

Provide verbal assurance that adequate birth control measures have been followed for 45 days prior to the first vaccine/placebo vaccination and will continue to be followed for at least 3 months after the final vaccine/placebo vaccination. More information on this criterion can be found in the protocol.

History of new onset, sexually acquired infection, as determined by local, syndromic diagnostics standards or, as available, serologic and microbiologic diagnosis within the 12 months prior to study entry

Has a known current high-risk partner or had such a partner within the 12 months prior to study entry

If a person has been diagnosed with high blood pressure during screening or previously, exclude for high blood pressure that is not well controlled. More information on this criterion can be found in the protocol.

If a person has NOT been diagnosed with high blood pressure during screening or previously, exclude for systolic blood pressure greater than or equal to 150 mm Hg at study entry or diastolic blood pressure greater than or equal to 100 mm Hg at study entry

Major psychiatric illness and/or substance abuse problems during the 12 months before study entry that, in the opinion of the investigator, would preclude study participation

Receipt of live attenuated vaccine within 30 days or inactivated/killed vaccine within 2 weeks of DNA vaccination

Use of experimental therapeutic agents within 30 days of study entry

Current or planned participation in another clinical study during the study period

Receipt of blood products or immunoglobulin in the 3 months before study entry

Recipient of an HIV vaccine candidate at any time and receipt of other experimental vaccine(s) within the 5 years before study entry. More information on this criterion can be found in the protocol.

A study site employee

Military personnel (will be excluded from participation in this study at all sites due to the potential for a false-positive HIV test result on mandatory HIV testing, which could have adverse affects on deployment status)

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01260727